In the late 1700s, Luigi Galvani observed a frog carcass move in response to electric stimulus. This led to the insight that cells are affected by and can transmit electrical signals. Two hundred years later, the patch clamp provided a way to study the electrical physiology of cells. See, e.g., Liem et al., 1995, The patch clamp technique, Neurosurgery 36(2):382-92.
The patch clamp technique can potentially illustrate processes such as signal transduction and synaptic transmission as well as consequences of conditions such as demyelination, brain and spinal cord injury, and cardiac arrhythmias—to give but a few examples. Unfortunately, the technique is remarkably difficult and time-consuming to implement. To set up a patch clamp, the tip of a glass pipette must be pushed against a patch of cell membrane and suction applied to create a clamp between the pipette and the patch. The patch ruptures, cytosol enters the pipette, and measurements are made in the pipette to determine the membrane electrical properties. Variations of this basic theme are known, but they all require the fundamentally difficult and limiting steps of physically clamping a pipette to a patch of cell membrane.